Implantable matrices have been used extensively to solve various medical problems in human and animal orthopedic surgical practices and their application has also extended to the field of cosmetic and reconstructive surgery, dental reconstructive surgery, and other medical fields involving surgery of hard and soft tissues.
Often times, to enhance growth of different cells within the implantable matrix and repair of tissue, a ligand is disposed on the implantable matrix and becomes available so that it can interact with a particular target receptor and cause the desired biological function. The formation and dissociation of specific noncovalent interactions between a ligand and its receptor plays a crucial role in the function of biological systems. The ligand and/or receptor of the matrix, in some embodiments, can stimulate other mammalian cell growth, such as for example, myocytes, cardiocytes to repair heart tissue, neuronal cells, or the like.
For example, when dealing with a ligand, such as bone morphogenic protein (BMP), it can be disposed on an implantable matrix and placed in a bone defect. BMP can be applied to the matrix before, during or after implantation. The BMP interacts with specific receptors on the cell surface, referred to as bone morphogenetic protein receptors (BMPRs). As persons of ordinary skill are aware the BMP spur the patient's body to begin the formation of new bone and/or cartilage growth. The BMP acts much like a catalyst, encouraging the necessary cells (including, but not limited to, mesenchymal stem cells, osteoblasts, and osteoclasts) to more rapidly migrate into the matrix, which is eventually resorbed via a cell-mediated process and newly formed bone is deposited at or near the bone defect. In this manner severe fractures may be healed, and vertebrae successfully fused.
Signal transduction through BMPRs also results in mobilization of members of the SMAD family of proteins. The signaling pathways involving BMPs, BMPRs and SMADs are also important in the development of the heart, and central nervous system tissue, as well as bone and cartilage.
Sometimes when too much ligand is applied to the matrix, or the surgeon manipulates the matrix to place it in the defect, excessive compression occurs causing increased amounts of ligand (e.g., bone morphogenic protein, TGF-alpha, TGF-beta, EGF, etc.) to leak from the matrix, which may reduce the stable microenvironment for cell growth, cause off target side effects (e.g., unwanted cell growth in other areas) or inhibit biological activity via a feedback inhibition. Sometimes too little ligand is applied to the matrix or the ligand on or in the matrix is depleted, which may also reduce the stable microenvironment for cell growth. Thus, there is a need to develop new matrices that have optimum ligand receptor concentrations.